Genetic predisposition of otosclerosis has long been suspected, but unclarified. Unique coexpression pattern of measles virus receptor (CD46) splicing isoforms in the human otic capsule is assumed, since otosclerosis is a measles virus-associated organ-specific disease. In order to identify CD46 involved in the pathogenesis of otosclerosis, we used representative groups of histologically diagnosed otosclerotic, nonotosclerotic, and normal stapes footplates . Consecutive histopathological examinations and CD46-specific Western blot analysis were performed. Normal and nonotosclerotic stapes footplates showed consistent expression of the conventional c, d, e, f, and l CD46 isoforms. In contrast, four novel isoforms (os1–4) translated as intact proteins were additionally detected in each otosclerotic specimen. The study herein presented provides evidence for the otosclerosis-associated expression pattern of CD46. This finding might explain the organ-specific, virus-associated and autoimmune-inflammatory pathogenesis of otosclerosis. Regarding our current knowledge, this is the first report that confirms the presence of four new disease-specific protein variants of CD46. 1. Introduction Otosclerosis is a complex inflammatory bone remodeling disorder of the human otic capsule that leads to progressive conductive and/or sensorineural hearing loss as a consequence of stapes footplate fixation and cochlear bone resorption with endosteal involvement [1]. In the Caucasian population, the prevalence of clinical otosclerosis is 0.3–0.4% of the general population, 5–9% of those with hearing loss, and 18–22% of those with conductive hearing loss [1, 2]. Silent otosclerotic foci are more common: histological otosclerosis without clinical symptoms has been reported as 8–11% in large unselected autopsy series [2]. Otosclerotic foci are limited to the temporal bone, and no lesions have been found outside of the ear [2–5]. Otosclerosis takes approximately two thirdS of stapes ankylosis cases leading to consecutive conductive hearing loss [6]. Differential diagnosis is still based on postoperative histological analysis of the removed stapes footplates [3, 4, 7]. However, several hypotheses suggest viral, autoimmune, and endocrine factors in the genesis of disease, etiopathogenesis of otosclerosis remained unexplained [3, 8–10]. Genetic factors must play a significant role in the etiopathogenesis of otosclerosis, although the precise mode of inheritance is still uncertain [3, 5, 10]. The potential etiologic role of measles virus in the pathogenesis of otosclerosis was
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